Haemophilia: overview and perspectives on gene therapy.
Keywords:
Genetics, Hemophilia A, Hemophilia B, factor IX, Factor VIII, Coagulation, Gene therapyAbstract
Introduction: Hemophilia is a disease that affects coagulation, produced by the deficiency of factors VIII and IX, which predisposes to hemophilia A and hemophilia B respectively. Currently, the management of hemophilia is carried out by controlling bleeding, by means of the application of coagulation factors or application of prophylaxis. To improve the care of people with hemophilia, gene therapy has been developed as a long-term treatment, through the editing of mutated genes, increasing serum levels and their activity, reducing bleeding and therefore enhancing the quality of life of patients. Objective: To describe the principal characteristics of hemophilia and gene therapy as an alternate treatment. Materials and methods: A review of the literature in Spanish and English was carried out in the Elsevier and PubMed databases, with the use of keywords such as “Hemophilia A”, “Hemophilia B”, “Factor IX”, Factor VIII ”, "Coagulation". Conclusions: Over the years, new treatments have been developed that allow improving the quality of life of patients with hemophilia, which can ultimately cure the disease in a definitive way, such as gene therapy, through non-pathogenic virus vectors for humans, allowing the editing of affected genes, hence increasing serum levels of coagulation factors.
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Lippi G, Favaloro EJ. Gene therapy for hemophilias: the end of phenotypic testing or the start of a new era? Blood Coagul Fibrinolysis. 2020;31(4):237-42. DOI: 10.1097/MBC.0000000000000905
Kloosterman F, Zwagemaker AF, Abdi A, Gouw S, Castaman G, Fijnvandraat K. Hemophilia management: huge impact of a tiny difference. Res Pract Thromb Haemost. 2020;4(3):377-85. DOI: 10.1002/rth2.12314
Ohmori T. Advances in gene therapy for hemophilia: basis, current status, and future perspectives. Int J Hematol. 2020;111(1):31-41. DOI: 10.1007/s12185-018-2513-4
World Federation of Hemophilia. Report on the Annual Global Survey 2019 [Internet]. Montréal: World Federation of Hemophilia; 2020 [citado 17 de noviembre 2020]. Disponible en: https://www.wfh.org/en/our-work-research-data/annual-global-survey
Mingot Castellano ME. General concepts on hemophilia A and on women carrying the disease. Blood Coagul Fibrinolysis. 2020;31(1S):S1-S3. DOI: 10.1097/MBC.0000000000000984
Donners AAMT, Maarseveen EM, Weetink YRJ, et al. Comparison between coagulation factor VIII quantified with one-stage activity assay and with mass spectrometry in haemophilia A patients: Proof of principle. Int J Lab Hematol. 2020;42(6):819-26. DOI: 10.1111/ijlh.13283
Nathwani AC. Gene therapy for hemophilia. Hematology Am Soc Hematol Educ Program. 2019;2019(1):1-8. DOI: 10.1182/hematology.2019000007
Reiss UM, Zhang L, Ohmori T. Hemophilia gene therapy-New country initiatives. Haemophilia. 2021;27 Suppl 3:132-141. DOI: 10.1111/hae.14080
World Federation of Hemophilia. Hemophilia in pictures [internet]. Montréal: World Federation of Hemophilia; 2020 [citado 17 de noviembre 2020]. Disponible en: http://www1.wfh.org/publications/files/pdf-1311.pdf
EAHAD Factor VIII Variant Database [Internet]. F8-db.eahad.org. 2020 [citado 23 Noviembre 2020]. Disponible en: https://f8-db.eahad.org/
Park C, Kim D, Son J, Sung J, Lee J, Bae S et al. Functional Correction of Large Factor VIII Gene Chromosomal Inversions in Hemophilia A Patient-Derived iPSCs Using CRISPR-Cas9. Cell Stem Cell. 2015;17(2):213-20. DOI: 10.1016/j.stem.2015.07.001
Eckhardt CL, van Velzen AS, Peters M, et al. Factor VIII gene (F8) mutation and risk of inhibitor development in nonsevere hemophilia A. Blood. 2013;122(11):1954-62.
EAHAD Factor IX Variant Database [Internet]. F9-db.eahad.org. 2020 [citado 23 Noviembre 2020]. Disponible en: https:// f9-db.eahad.org/
Goodeve AC. Hemophilia B: molecular pathogenesis and mutation analysis. J Thromb Haemost. 2015;13(7):1184-95. DOI: 10.1111/jth.12958
Rallapalli PM, Kemball-Cook G, Tuddenham EG, Gomez K, Perkins SJ. An interactive mutation database for human coagulation factor IX provides novel insights into the phenotypes and genetics of hemophilia B. J Thromb Haemost. 2013;11(7):1329-40. DOI: 10.1111/jth.12276
Blanchette VS, Key NS, Ljung LR, et al. Definitions in hemophilia: communication from the SSC of the ISTH. J Thromb Haemost. 2014;12(11):1935-9. DOI: 10.1111/jth.12672
Salen P, Babiker HM. Hemophilia A. 2020 Nov 19. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020.
Peyvandi F, Garagiola I, Young G. The past and future of haemophilia: diagnosis, treatments, and its complications. Lancet. 2016;388(10040):187-97. DOI: 10.1016/S0140-6736(15)01123-X
Nathwani AC, Davidoff AM, Tuddenham EGD. Gene Therapy for Hemophilia. Hematol Oncol Clin North Am. 2017;31(5):853-68. 10.1182/hematology.2019000007
Manco-Johnson MJ, Abshire TC, Shapiro AD, Riske B, Hacker MR, Kilcoyne R, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med. 2007;357(6):535-44. DOI: 10.1056/NEJMoa067659
Batty P, Lillicrap D. Advances and challenges for hemophilia gene therapy. Hum Mol Genet. 2019;28(R1):R95-R101. DOI: 10.1093/hmg/ddz157
Miesbach W, O’Mahony B, Key NS, Makris M. How to discuss gene therapy for haemophilia? A patient and physician perspective. Haemophilia. 2019;25(4):545-557. DOI: 10.1111/hae.13769
Smith CIE, Blomberg P. Genterapi – från idé till verklighet - Ännu har få patienter behandlats och preparaten är ofta mycket dyra – men utvecklingen går fort nu [Gene therapy – from idea to reality]. Lakartidningen. 2017;114:EWYL. Swedish.
Lambert T, Benson G, Dolan G, Hermans C, Jimenez-Yuste V, Ljung R, et al. Practical aspects of extended half-life products for the treatment of haemophilia. Ther Adv Hematol. 2018;9(9):295-308. DOI: 10.1177/2040620718796429
US Food and Drug Administration. FDA approves new treatment to prevent bleeding in certain patients with hemophilia A. 2018. Disponible en: https ://www.fda.gov/newse vents/ newsr oom/press annou ncements/ucm58 5567.htm. Accessed October 26, 2018.
Oldenburg J, Mahlangu JN, Kim B, et al. Emicizumab Prophylaxis in Hemophilia A with Inhibitors. N Engl J Med. 2017;377(9):809-18. DOI: 10.1056/NEJMoa1703068
Mahlangu J, Oldenburg J, Paz-Priel I, et al. Emicizumab Prophylaxis in Patients Who Have Hemophilia A without Inhibitors. N Engl J Med. 2018;379(9):811-22. DOI: 10.1056/NEJMoa1803550
Nienhuis AW, Nathwani AC, Davidoff AM. Gene Therapy for Hemophilia. Mol Ther. 2017;25(5):1163-67. DOI: 10.1016/j.ymthe.2017.03.033
Bhardwaj R, Rath G, Goyal AK. Advancement in the treatment of haemophilia. Int J Biol Macromol. 2018;118(Pt A):289-295. DOI: 10.1016/j.ijbiomac.2018.06.084
Kaczmarek R. Terapia genowa hemofilii – czy wkrótce będzie możliwe wyleczenie? [Gene therapy of haemophilia - has the cure come within reach?]. Postepy Biochem. 2018;64(4):318-22. DOI: 10.18388/pb.2018_145.
Peyvandi F, Garagiola I. Clinical advances in gene therapy updates on clinical trials of gene therapy in haemophilia. Haemophilia. 2019;25(5):738-746. DOI: 10.1111/hae.13816
VandenDriessche T, Chuah MK. Hemophilia Gene Therapy: Ready for Prime Time? Hum Gene Ther. 2017;28(11):1013-1023. DOI: 10.1089/hum.2017.116
Herzog RW, Hagstrom JN, Kung SH, Tai SJ, Wilson JM, Fisher KJ, et al. Stable gene transfer and expression of human blood coagulation factor IX after intramuscular injection of recombinant adeno-associated virus. Proc Natl Acad Sci U S A. 1997;94(11):5804-9. DOI: 10.1073/pnas.94.11.5804
Kay MA, Manno CS, Ragni M V, et al. Evidence for gene transfer and expression of factor IX in haemophilia B patients treated with an AAV vector. Nat Genet. 2000;24(3):257-61. DOI: 10.1038/73464
Herzog RW, Yang EY, Couto LB, et al. Long-term correction of canine hemophilia B by gene transfer of blood coagulation factor IX mediated by adeno-associated viral vector. Nat Med. 1999;5(1):56-63. DOI: 10.1038/4743
Kay MA, Rothenberg S, Landen CN, Bellinger DA, Leland F, Toman C, et al. In vivo gene therapy of hemophilia B: sustained partial correction in factor IX-deficient dogs. Science. 1993;262(5130):117-9. DOI: 10.1126/science.8211118
Kaiser J. Gene therapy. Side effects sideline hemophilia trial. Science. 2004;304(5676):1423-5. DOI: 10.1126/science.304.5676.1423b
Gura T. Hemophilia. After a setback, gene therapy progresses...gingerly. Science. 2001;291(5509):1692-7. DOI: 10.1126/science.291.5509.1692
Rangarajan S, Walsh L, Lester W, et al. AAV5-Factor VIII Gene Transfer in Severe Hemophilia A. N Engl J Med. 2017;377(26):2519-2530. DOI: 10.1056/NEJMoa1708483
Rodriguez-Merchan EC. What´s new in Gene Therapy of Hemophilia. Curr Gene Ther. 2018;18(2):107-114. DOI: 10.2174/1566523218666180214162312
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